Many cells and microorganisms require light for growth and/or production of secondary metabolites. Similarly, cells and microorganisms capable of photosynthesis require light for the fixation of carbon dioxide and the production of oxygen. Thus, the efficient growth of photo-autotrophic cells and the efficient production of oxygen from carbon dioxide by photosynthetic cells present the need for photobioreactors.
In addition, one of the more important challenges in achieving manned flight in space for prolonged periods of time is to have an on-line workable and efficient closed ecological life support system (CELSS) which provides oxygen, food, and water for humans and recycles wastes. Many life support systems have been designed that use algal cell cultures to produce oxygen (see, e.g., Krauss, in Life Science and Space Research, Pergamon press, Holmquist, ed., New York, pp. 13-26 (1978); Miller et al, USAF School of Aerospace Medicine, SAMTR-66-11 (1966); and Wharton et al, in Algae and Human Affairs, Lembi and Waalend, eds., Cambridge University Press, pp. 486-509 (1988)). Algal cultures are primary candidates for inclusion in a bioregenerative system because; they typically grow rapidly, have metabolism that can be controlled, produce a high ratio of edible to nonedible biomass, and have gas-exchange characteristics compatible with human requirements (see Wharton et al). Successful utilization of microalgae in a CELSS requires an energy efficient and compact photobioreactor.
The issues to be addressed in an efficient design include; optimal lighting techniques and configurations with an emphasis on lighting efficiency; gravity independent gasliquid separation; minimal heat transfer; and minimal cell adherence to the surface (Averseer et al, NASA Contractor Report, 166615 (1984)) . Some of these problems such as optimal lighting techniques and selection of appropriate wavelengths have already been addressed (Mori, in Symposium on Biotechnology for Fuels and Chemicals, vol. 7, pp. 331-345 (1985)). In the bioreactor of Mori, a plurality of fiberoptic light radiators are immersed within a tank. However, the problem of keeping the cells in suspension is not addressed in this apparatus. Also, the main concern of the design of Mori is to provide light of the right quality for the culture. In the present photobioreactor, the illumination source is outside the irradiation chamber, while the illumination takes place inside the chamber.
U.S. Pat. No. 4,868,123 to Berson et al discloses an apparatus for the controlled production of microorganisms in which a group of transparent tubes are placed on an expanse of water. However, the apparatus of Berson et al relies on solar rather than artificial light sources.
For the last decade, membrane lungs have been used extensively for prolonged extracorporeal life support (ECLS), particularly for neonatal respiratory failure and cardiac or pulmonary failure in children and adults. Extracorporeal life support has also been used on occasion as a bridge for lung transplantation. The two techniques of ECLS and lung transplantation should be complementary like hemodialysis and renal transplantation. Unfortunately, immune suppression is generally considered to be contraindicated in ECLS, because of bacterial infection and a low rate of successful recovery. Even if infectious complications could be solved, prolonged ECLS is an invasive procedure and is thus used only with patients who require high pressure, high oxygen mechanical ventilation, a situation generally considered to be contraindicated in lung transplantation. Thus, in the current state of the art, a problem faces both prolonged ECLS and lung transplantation.
The solution to the problem is the implantable artificial lung. However, the concept has never been evaluated in a clinical setting and very rarely tested in the animal laboratory. The major probems are in the thrombosis/microembolism in the blood phase and water accumulation in the gas phase with the membrane lung, as well as the requirement of an external gas tank for continuous supply of a high flow of 100% oxygen. Hence, the concept of the implantable lung as a support system, or as a bridge to transplantation, is at a stalemate using the current technology.
The development of artificial lungs has progressed from filming, foaming, and bubble oxygenators to membrane lungs which simulate the alveolus. Membrane lungs may be fabricated from solid silicone "rubber" polymer or from microporous material (Kolobow T, Bowman R L: Construction and evaluation of an alveolar membrane artificial heart lung, Trans. Am. Soc. Artif. Intern. Organs, 9: 238-247, 1963). For the last decade, membrane lungs have been used extensively for prolonged extracorporeal support, particularly for newborn respiratory failure. Based largely on the safety and efficacy of membrane lungs for days or weeks of chronic support, the use of membrane lungs for cardiac surgery has steadily grown during the last decade so that now more than 60% of cardiac surgical operations are done using membrane lungs. Prolonged extracorporeal life support (ECLS) for cardiac or pulmonary failure has become standard treatment for neonatal respiratory failure and has been used in many centers for prolonged cardiac or pulmonary failure in children and adults. Survival rates are 90% for newborn infants and 50% for children and adults (Dennis C: A heart lung machine for open-heart operation: How it came about, Trans. Am. Soc. Artif. Intern, Organs 35: 767-777, 1989). Extracorporeal life support cases commonly run for more than three weeks of time without major deleterious effects (Glass P, Miller M, Short B: Morbidity for survivors of extracorporeal membrane oxygenation: Neurodevelopmental outcome at 1 year of age, Pediatrics 83: 72-78, 1989). Almost all of this experience (now totaling greater than 4500 cases) has been achieved with the solid silicone rubber SciMed Kolobow membrane lung (Stolar C J, Snedecor S S, Bartless R H: Extracorporeal membrane oxygenation and neonatal respiratory failure: Experience from the extracorporeal life support organization, J. Pediatric Surg., in press). Although the membrane lung may malfunction and require changing after one to two weeks, there are many examples of membrane lungs which have worked successfully for three weeks or more. The major problems with membrane lungs are thrombosis and/or microembolism in the blood phase and water accumulation in the gas phase. The thrombosis problem is generally well controlled with continuous low dose systemic heparinization (Kolobow T: Gas exchange with membrane lungs, in Neonatal and Adult Respiratory Failure: Mechanisms and Treatment (Gille M, Ed.) pp 89-96, Elsevier, Paris, 1989). Recently, the use of heparin bonded membrane lungs has been successfully used without heparin in the laboratory and clinical trials are currently underway (Toomasian J M, Hsu L C, Hirschl R B, Hultquist K A: Evaluation of Duraflo II heparin coating in prolonged extracorporeal membrane oxygenation, Trans, Am. Soc. Artif. Intern. Organs 34: 410-414, 1988). The problem of water accumulation in the gas phase can be minimized by using a high gas flow rate. Heating and humidifying the gas has been reported to decrease the water accumulation. However, this will always be a potential problem with membrane lungs of the current design (Mottaghy K, Oedekoven B, Poppel K, et al: Heparin free long-term extracorporeal circulation using bioactive surfaces, Trans. Am. Soc. Artif. Intern. Organs 35: 635-635, 1989).
During the last five years, lung transplantation has grown from an occasional clinical curiosity to well a established clinical investigation and application in many centers. Lung transplantation has proven to be quite successful when it is applied in stable patients, who are not acutely ill and not on mechanical ventilators. The problems limiting lung transplantation are the availability of suitable donors and the fact that infectious complications are prohibitive when the recipient patients are critically ill on mechanical ventilation. Unfortunately, many patients who might benefit from lung transplantation are in the latter category. Another problem with lung transplantation is the early pulmonary failure that can occur secondary to ischemic time, reperfusion, or other causes of capillary leakage in the recently transplanted lung. This problem could possibly be successfully managed with ECLS, but immune suppression is generally considered to be contraindicated in ECLS because of bacterial infection and a low rate of successful recovery.
Extracorporeal life support has been used on occasion as a bridge to lung transplantation and the technique is certainly feasible. The two techniques of ECLS and lung transplantation should be complementary like hemodialysis and renal transplantation. Unfortunately, unlike hemodialysis in which the patient is on the procedure only a few times a week, ECLS requires the patient to be continuously immobilized to the machine. Even if the infectious complications could be solved, prolonged extracorporeal support is labor intensive, expensive, and subject to mechanical breakdown of the pumping system, not to mention the membrane lung problems described above. In addition, ECLS is a more invasive procedure as compared to that of hemodialysis. These problems render ECLS to be used only with patients who require high pressure, high oxygen mechanical ventilation, a situation generally considered to be contraindicated in lung transplantation. The problems discussed above have been reviewed in detail in a recent article published by Bartlett, R H: Current Problems in Surgery, in: Extracorporeal Life Support Cardiopulmonary Failure (Wells, Jr., SA, Ed.), Vol. XXVII, No. 10, pp. 627-705, Mosby-Year Book, St. Louis, Mo. 1990.
With current technology, a relatively small artificial lung with low blood flow resistance can be placed in the left chest adjacent to the native lung with end to side vascular anastomosis to the pulmonary artery and left atrium. Technically, it is relatively simple to place such a device in experimental animals and patients with either chronic or acute pulmonary failure, leaving the native lungs in place without disturbing the anatomy at the hilum of the lung, allowing subsequent transplantation, continued support as needed with the implantable lung, then removal of the implantable device. Both in concept and practice, this procedure is simpler and less disruptive than the placement of an implantable ventricular assist device or bridging artificial heart. However, the implantable lung concept has never been evaluated in a clinical setting and very rarely tested in the animal laboratory. The reason is that the useful life of currently available membrane lungs is approximately one week. Even if artificial lungs could function successfully for three or four weeks this would not be sufficient to justify the major operation of thoracotomy and implantation. To be successful for bridging to transplantation, an implantable lung would have to function for one to six months without changing the membrane lung. Of the two problems limiting prolonged function of membrane lungs, the solution to the thrombosis problem appears to be close at hand. The combination of heparin bonded surface, platelet inhibiting drugs, and careful attention to rheologic design, makes thrombosis a rare occurrence, even in the complex extracorporeal life support systems. A more significant problem for an implantable membrane lung is the gas phase. Membrane lungs require 100% oxygen at relatively high flow rates which must be continuously supplied. This requires transcutaneous gas entry and exit lines, running the risk of infection, and requiring a continuous high flow of 100% oxygen. More importantly, the accumulation of water in the gas phase with gradual loss of membrane lung function limits the useful life of membrane lungs. Even if all the above problems could be solved, the patients would still likely be secured to the oxygen supply, require intensive care, and suffer high medical costs (e.g., the costs of labor and oxygen supply).
Thus, there remains a need for photobioreactors which can achieve the efficient growth of photo-autotrophic or mixo-trophic cells and the efficient production of oxygen from carbon dioxide. In addition, there remains a need for a practical artificial lung.